Good news. No matter whether their autoimmune theory holds up, it definitely puts CFS into somatic (body) disease. The fact that tinkering with the immune system can have such dramatic effects is a big clue and will lead to an increase in other research. Even more, we have another drug company interested in our illness. Maybe this one can make advances more quickly.

Overall, ever since the 2009 study, the debates have been virus or autoimmune or other immune or neurological. Except for the PACE blip, the rest of the research world has tuned into which biological / physiological abnormality is the first to be diseased.

And we now have big boys interested. Research / physician centers are popping up like pop corn. Money, $10 million from a family foundation. Who would have thunk it four years ago?

This study is only of 30 people and of the 15 that received the drug, only 10 saw major improvements. Some patients have come out saying their experience was anything but good. This is also the case with Ampligen, which has good results in some, but detrimental to others. Although this study says no side effects, reading the list is scary, including sudden death. On the other side, it is used for many different illnesses, including RA, MS, lupus and as a chemo treatment. So the history of it in other illnesses should be well-known.

It's a roller coaster. And it just went up again. Hold on for the ride folks.

This is a response to Kati. Indeed, patients in Canada would have to organize and ask for compassionate access to this drug. However, as you may know the Canadian medical system is crumbling. Many folks do not have a family doctor. Furthermore, treatments for complex illnesses are simply not available. I don't want to stray off the topic of this announcement today by the Norwegian physicians. But I do want to mention that the system in Canada is in crises--although folks elsewhere often are not aware of what is happening. And middle upper class and upper class folks go to the US or to Europe for treatment. It may have to do with the small population and the skyrocketing prices in medical care, not to mention inefficiency, but I suspect the Canadian government would baulk at requests for this med. A highly mobilized organization of people might make some difference, but it would take a dog's age.

Click to expand...

Helene, this is for you. I have been in said health care system from the point of view of a nurse. I have worked in a state of the art building that offers care for cancer patients. PET scanner, MRI, first class research, clinical trials go on in this center. There is a huge building which is a cancer foundation. It is made of glass and looks like they have lots of money. (you could argue this is donated money). Patients have access to a volunteer system who come and pick them up at their doorstep (as far as 100 Km) for their apt and will take them back home. Dying patients get chemotherapy given to them for palliation of their symptoms. Their doctors agree to very expensive drugs that is not given for their tumor sites under a program called compassionate access. Dying patients get dialysis if the family wants to, even if the patient is not conscious and there is no hope to get this poor person back alive.

There is a lot of money for cancer. There is money for spinal cord injury. There is money for trauma. There is still lots of money for MS research. Lots of money for HIV/AIDS. Diabetes. What about ME? We do have the right to health care, crumbling system or not. So Helene, if you want to same the health care system, you can stay home. It is in my opinion that I am entitled to health care in Canada. I will see one specialist after the next until I get what I need.

The Rituximab story is a good one to argue to our government because it is already administered to many different diseases. Who prescribes it? Oncologists and Rheumatologists do.

Do we, patient with ME have the right to health care? Yes, just the same as cancer patients and AIDS patients, and the rest of them. That is my opinion, and you are certainly entitled to yours.

I'm Skeptical, This all started because they had a patient who had Hodgkins lymphoma and also had a diagnosis of CFS. Which as a side note just goes to show what a Wastebasket diagnosis CFS is. Applying a CFS diagnosis to Hodgkin's Lymphoma which has severer fatigue as a component is absurd. It completely defeats the purported purpose of even creating CFS to begin with. But I digress.

It just seems funny that the whole JM & WPI XMRV issue involved a retrovirus that is purported to have an association with a type of cancer. So we now have these doctors who give someone with Lymphoma who also has the Diagnosis of CFS Rituximab.

Now if ME which is what many with the CFS diagnosis have is caused by a retrovirus that can cause or play a role in the development of cancer or various cancers. Then it seems that giving this drug could and would act as a mask (if you will) and as a result you run the risk of not looking for cancers which could have deadly results for the patient.

But we'll easily know if this is part of the establishment agenda towards ME/CFS. If The usually suspects begin to attack those Doctors their assertions and this potential treatment then we'll have our answer.

Check this out--about Rituximab and kidneys. It is one of a number of articles about how Rituximab helps restore both kidneys in a state of disease as well as helping with kidney transplants. YAY! My kidneys have sunk into the diseased category, which I have read is found often in ME/CFS, according to a South Korean doctor who runs a clinic for ME/CFS.

Nice. But you know what bugs me? The Answer autoimmun disease. Thats basically another word for we don't know. There so many autoimmun diseases out there and still new stuff appears to be cause by autoimmun diseases. And noone knows whats causing this. Personally I don't see autoimmun disease as a real answer.

Click to expand...

True about autoimmunity being poorly understood but by being in a disease category that receives mounds of biomedical research funds is much better than being in a new/unknown disease category that receives next to nothing.

A treatment that works for an unknown reason is an excellent interim measure.

Many diseases do not have a known ultimate cause and it is not necessary to have an ultimate cause, in order to be a legitimate disease (ME has a double standard applied to it).

However, I think the search for the cause of ME (propelled by the unfair double standard), has the potential to help many, many other devastating diseases, which have "settled" for knowing some intermediate pathology and don't necessarily look for an ultimate cause.

We need both. Right now, treatment for intermediate pathology or treatment that works for unknown reasons (I am not picky; I just want my life back!).

And as soon as can be managed, a better understanding of the entire pathology including ultimate cause. Whether that's mold, an exogenous retrovirus, an endogenous retrovirus, enterovirus, a variety of infections including HHV-6 variant a, methylation block, something we haven't thought of or even haven't discovered at all, or different things for different ones of us.

I think this is a very interesting development, and I want to suggest what I think is going on when Rituximab is used to treat ME/CFS.

It will probably come as no surprise to those familiar with my history here that I will propose a mechanism that fits with the GD-MCB hypothesis for the pathophysiology of ME/CFS.

O.K., here it goes:

Based on the body of immunological studies that have been done in ME/CFS over quite a few years, we know that the immune system is dysfunctional in this disorder. In particular, it has a pronounced shift to the Th2 type of response, away from cell-mediated immunity.

The NK cells and the cytotoxic (CD8) killer-T cells are ineffective, partly because they are unable to produce enough perforin to punch holes in cells that are infected with viruses. Since this is the main mechanism normally used to knock out viral infections, these infections cannot be knocked out.

The immune system is forced to use its fall-back mechanisms, which are the humoral immune response (antibodies produced in Th2 by the B cells, which become plasma cells), and the interferon-induced mechanisms, including RNase-L.

These are less effective and are not able to completely knock out viral infections (The cell-mediated cavalry never arrives). This is the reason for the ongoing guerrilla war in the person's body, with both the reactivated viruses which have been in the body in the latent state, and with new ones that come along and infect the person after the onset of ME/CFS

As has been noted, the B cells do produce proinflammatory cytokines, which of course promote inflammation. Because most PWCs also have a dysfunctional HPA axis, cortisol tends to be low, and the inflammation is allowed to intensify to a higher level than normal.

Note that one of the main features of inflammation is oxidative stress, because cells of the immune system produce oxidizing species to attack the body's enemies. Oxidative stress is well-documented in ME/CFS, with perhaps 20 published papers reporting evidence of it now.

And those familiar with the body's antioxidant system will know that when a state of oxidative stress is present, the antioxidant system is losing the battle between oxidants and antioxidants.

Those familiar will also know that glutathione is the basis of the antioxidant enzyme system in the body. So now we come to realize that in the subset of PWMEs/PWCs in whose bodies infection is a major aspect of their illness, we can expect that a major part of the oxidative stress, and hence a major part of the demand on glutathione, will be due to inflammation, which is being stimulated by the B cells in the overactive Th2 immune response.

O.K., so now we put in Rituximab, which kills the B cells. What happens?

Well, the inflammatory cytokines drop down, as does inflammation. This lowers the oxidative stress, taking a big demand off glutathione, which is then able to rise to at least some degree.

Aficionados of the GD-MCB hypothesis will immediately suspect that a big part of the symptomatology of ME/CFS will diminish, since the causes of a large fraction, perhaps the majority, of ME/CFS symptoms can be traced directly to the depletion of glutathione.

So voila! The patient feels better, until her/his B cells grow back, and the whole process repeats itself, making her/him miserable again. So we hit the patient with another dose of Rituximab, and she/he bounces back up, and so on. If we do succeed in permanently devastating the B cells, what happens in the longer term? Certainly they were there for a purpose. Will the body be adequately defended against its enemies in the future? I think that's a big question.

The main point I want to make is that this treatment, like many others that have been used or proposed for ME/CFS, addresses a down-stream issue in the pathophysiology, and does not get to the root of the problem, which I believe (and have evidence to support this belief) is a vicious circle mechanism that includes glutathione depletion, a functional deficiency of vitamin B12, a partial block of methionine synthase in the methylation cycle, and draining of folates from the cells. So far, the only way it seems to be possible to break this vicious cycle is to lift the partial block in the methylation cycle with appropriate treatment that includes simultaneous use of active forms of folate and high dosage of forms of vitamin B12. Among other effects, this should rebalance the immune system, so that the B cells as well as the other components of the immune system will return to their normal functions. I do need to add that some other things will likely need to be done as well to help this process along, and which things will depend on the details of each case. But lifting the partial methylation cycle block is the fundamental thing that needs to be done.

I would welcome any criticisms of this proposed mechanism. As far as I can tell, everything fits together well.

If anyone wants to get more information on the GD-MCB hypothesis, I recommend watching the video at

I think this is a very interesting development, and I want to suggest what I think is going on when Rituximab is used to treat ME/CFS.

It will probably come as no surprise to those familiar with my history here that I will propose a mechanism that fits with the GD-MCB hypothesis for the pathophysiology of ME/CFS.

O.K., here it goes:

Based on the body of immunological studies that have been done in ME/CFS over quite a few years, we know that the immune system is dysfunctional in this disorder. In particular, it has a pronounced shift to the Th2 type of response, away from cell-mediated immunity.

The NK cells and the cytotoxic (CD8) killer-T cells are ineffective, partly because they are unable to produce enough perforin to punch holes in cells that are infected with viruses. Since this is the main mechanism normally used to knock out viral infections, these infections cannot be knocked out.

The immune system is forced to use its fall-back mechanisms, which are the humoral immune response (antibodies produced in Th2 by the B cells, which become plasma cells, and the interferon-induced mechanisms, including RNase-L).

These are less effective and are not able to completely knock out viral infections (The cell-mediated cavalry never arrives). This is the reason for the ongoing guerrilla war in the person's body, with both the reactivated viruses which have been in the body in the latent state, and with new ones that come along and infect the person after the onset of ME/CFS

As has been noted, the B cells do produce proinflammatory cytokines, which of course promote inflammation. Because most PWCs also have a dysfunctional HPA axis, cortisol tends to be low, and the inflammation is allowed to intensify to a higher level than normal.

Note that one of the main features of inflammation is oxidative stress, because cells of the immune system produce oxidizing species to attack the body's enemies. Oxidative stress is well-documented in ME/CFS, with perhaps 20 published papers reporting evidence of it now.

And those familiar with the body's antioxidant system will know that when a state of oxidative stress is present, the antioxidant system is losing the battle between oxidants and antioxidants.

Those familiar will also know that glutathione is the basis of the antioxidant enzyme system in the body. So now we come to realize that in the subset of PWMEs/PWCs in whose bodies infection is a major aspect of their illness, we can expect that a major part of the oxidative stress, and hence a major part of the demand on glutathione, will be due to inflammation, which is being stimulated by the B cells in the overactive Th2 immune response.

O.K., so now we put in Rituximab, which kills the B cells. What happens?

Well, the inflammatory cytokines drop down, as does inflammation. This lowers the oxidative stress, taking a big demand off glutathione, which is then able to rise to at least some degree.

Aficionados of the GD-MCB hypothesis will immediately suspect that a big part of the symptomatology of ME/CFS will diminish, since the causes of a large fraction, perhaps the majority, of ME/CFS symptoms can be traced directly to the depletion of glutathione.

So voila! The patient feels better, until her/his B cells grow back, and the whole process repeats itself, making her/him miserable again. So we hit the patient with another dose of Rituximab, and she/he bounces back up, and so on. If we do succeed in permanently devastating the B cells, what happens in the longer term? Certainly they were there for a purpose. Will the body be adequately defended against its enemies in the future? I think that's a big question.

The main point I want to make is that this treatment, like many others that have been used or proposed for ME/CFS, addresses a down-stream issue in the pathophysiology, and does not get to the root of the problem, which I believe (and have evidence to support this belief) is a vicious circle mechanism that includes glutathione depletion, a functional deficiency of vitamin B12, a partial block of methionine synthase in the methylation cycle, and draining of folates from the cells. So far, the only way it seems to be possible to break this vicious cycle is to lift the partial block in the methylation cycle with appropriate treatment that includes simultaneous use of active forms of folate and high dosage of forms of vitamin B12. Among other effects, this should rebalance the immune system, so that the B cells as well as the other components of the immune system will return to their normal functions. I do need to add that some other things will likely need to be done as well to help this process along, and which things will depend on the details of each case. But lifting the partial methylation cycle block is the fundamental thing that needs to be done.

I would welcome any criticisms of this proposed mechanism. As far as I can tell, everything fits together well.

If anyone wants to get more information on the GD-MCB hypothesis, I recommend watching the video at

I'm Skeptical, This all started because they had a patient who had Hodgkins lymphoma and also had a diagnosis of CFS. Which as a side note just goes to show what a Wastebasket diagnosis CFS is. Applying a CFS diagnosis to Hodgkin's Lymphoma which has severer fatigue as a component is absurd. It completely defeats the purported purpose of even creating CFS to begin with. But I digress.

It just seems funny that the whole JM & WPI XMRV issue involved a retrovirus that is purported to have an association with a type of cancer. So we now have these doctors who give someone with Lymphoma who also has the Diagnosis of CFS Rituximab.

Now if ME which is what many with the CFS diagnosis have is caused by a retrovirus that can cause or play a role in the development of cancer or various cancers. Then it seems that giving this drug could and would act as a mask (if you will) and as a result you run the risk of not looking for cancers which could have deadly results for the patient.

But we'll easily know if this is part of the establishment agenda towards ME/CFS. If The usually suspects begin to attack those Doctors their assertions and this potential treatment then we'll have our answer.

Click to expand...

+1

This supports the retrovirus as a root cause. Retrovirii cause cancer. I sometimes think of ME as "slow cancer". So a cancer treatment may appear to help but may not be the root cause. Still, good news.

From Wikipedia. The term somatic (from the Greek ?????????) means 'of the body',[1], relating to the body. In medicine, somatic illness is bodily, not mental, illness.

What Max said. I'm Canadian... I could probably stand the Norwegian winter. And heck, if my ME/CFS husband improved we could xc ski again. In the meantime I think I'll try to dig up someone at the local university (UofAlberta - Judy had an interesting meeting here, and I'm hoping her comment about Canadian institution might have been one here) and see if anyone wants to do a trial, as surely this won't come through our regular, crumbling, system.

and, hmmmmm. Your thinking still fascinates Rich and I have been trying to get a doc here interested in supporting John through it. Maybe a bit of Rituximab to gather some strength and courage,(both of which are rather depleted) then get to work on the methylation cycle?

I think this is a very interesting development, and I want to suggest what I think is going on when Rituximab is used to treat ME/CFS.

It will probably come as no surprise to those familiar with my history here that I will propose a mechanism that fits with the GD-MCB hypothesis for the pathophysiology of ME/CFS.

O.K., here it goes:

Based on the body of immunological studies that have been done in ME/CFS over quite a few years, we know that the immune system is dysfunctional in this disorder. In particular, it has a pronounced shift to the Th2 type of response, away from cell-mediated immunity.

The NK cells and the cytotoxic (CD8) killer-T cells are ineffective, partly because they are unable to produce enough perforin to punch holes in cells that are infected with viruses. Since this is the main mechanism normally used to knock out viral infections, these infections cannot be knocked out.

The immune system is forced to use its fall-back mechanisms, which are the humoral immune response (antibodies produced in Th2 by the B cells, which become plasma cells, and the interferon-induced mechanisms, including RNase-L).

These are less effective and are not able to completely knock out viral infections (The cell-mediated cavalry never arrives). This is the reason for the ongoing guerrilla war in the person's body, with both the reactivated viruses which have been in the body in the latent state, and with new ones that come along and infect the person after the onset of ME/CFS

As has been noted, the B cells do produce proinflammatory cytokines, which of course promote inflammation. Because most PWCs also have a dysfunctional HPA axis, cortisol tends to be low, and the inflammation is allowed to intensify to a higher level than normal.

Note that one of the main features of inflammation is oxidative stress, because cells of the immune system produce oxidizing species to attack the body's enemies. Oxidative stress is well-documented in ME/CFS, with perhaps 20 published papers reporting evidence of it now.

And those familiar with the body's antioxidant system will know that when a state of oxidative stress is present, the antioxidant system is losing the battle between oxidants and antioxidants.

Those familiar will also know that glutathione is the basis of the antioxidant enzyme system in the body. So now we come to realize that in the subset of PWMEs/PWCs in whose bodies infection is a major aspect of their illness, we can expect that a major part of the oxidative stress, and hence a major part of the demand on glutathione, will be due to inflammation, which is being stimulated by the B cells in the overactive Th2 immune response.

O.K., so now we put in Rituximab, which kills the B cells. What happens?

Well, the inflammatory cytokines drop down, as does inflammation. This lowers the oxidative stress, taking a big demand off glutathione, which is then able to rise to at least some degree.

Aficionados of the GD-MCB hypothesis will immediately suspect that a big part of the symptomatology of ME/CFS will diminish, since the causes of a large fraction, perhaps the majority, of ME/CFS symptoms can be traced directly to the depletion of glutathione.

So voila! The patient feels better, until her/his B cells grow back, and the whole process repeats itself, making her/him miserable again. So we hit the patient with another dose of Rituximab, and she/he bounces back up, and so on. If we do succeed in permanently devastating the B cells, what happens in the longer term? Certainly they were there for a purpose. Will the body be adequately defended against its enemies in the future? I think that's a big question.

The main point I want to make is that this treatment, like many others that have been used or proposed for ME/CFS, addresses a down-stream issue in the pathophysiology, and does not get to the root of the problem, which I believe (and have evidence to support this belief) is a vicious circle mechanism that includes glutathione depletion, a functional deficiency of vitamin B12, a partial block of methionine synthase in the methylation cycle, and draining of folates from the cells. So far, the only way it seems to be possible to break this vicious cycle is to lift the partial block in the methylation cycle with appropriate treatment that includes simultaneous use of active forms of folate and high dosage of forms of vitamin B12. Among other effects, this should rebalance the immune system, so that the B cells as well as the other components of the immune system will return to their normal functions. I do need to add that some other things will likely need to be done as well to help this process along, and which things will depend on the details of each case. But lifting the partial methylation cycle block is the fundamental thing that needs to be done.

I would welcome any criticisms of this proposed mechanism. As far as I can tell, everything fits together well.

If anyone wants to get more information on the GD-MCB hypothesis, I recommend watching the video at

The slides from the talk are available there too, if you don't want to hang in for the whole 3-plus hours.

Best regards,

Rich

Click to expand...

Rich, whether your glutathione theory is correct or not, I think this points out that there may be more than one way to interpret their results. They are saying that this suggests that ME/CFS is an autoimmune disorder, but I think that's a pretty big leap of logic. We know that parts of the immune system are activated above normal. We also know that some of the over-activated parts are what turn on the so-called "sickness behavior" in the brain: that is, the signals that tell us we're sick and make us feel lousy. It stands to reason that if you shut down those parts of the immune system, we'll feel better. But it doesn't really tell us WHY those parts of the immune response are up-regulated. If they are up-regulated in response to a persistant pathogen (or combination of pathogens), shutting down the immune system could make us feel better in the short-term, but leave us less able to fight the pathogen.

I'm not saying that's what's happening, just that it's another possible explanation.

The results of this trial are intriguing, but I would be very hesitant to take a drug to shut down parts of the immune system without a lot more evidence of what's going on. I think that their autoimmune theory is just one of several plausible explanations for the results they got. It doesn't explain things like why ME/CFS patients don't have an abnormal antinuclear antibody (ANA) test.

I think that this one will be trumpeted as a big breakthrough because it is a drug that they own the patent to, so they could make a lot of money if it works. But because drug companies' job is to make money, they don't always look too closely at the long-term effects of their drugs on patients. I think we need to approach this one very cautiously.

Which as a side note just goes to show what a Wastebasket diagnosis CFS is. Applying a CFS diagnosis to Hodgkin's Lymphoma which has severer fatigue as a component is absurd.

Click to expand...

Not necessarily. There have been reports of higher than normal incidence of lymphoma in ME/CFS patients. Dr Peterson noticed that with his Incline Village patients. If someone had had ME/CFS for a long while and then developed lymphoma, that wouldn't cancel out the ME/CFS diagnosis. And if the cancer treatment also cleared up the ME/CFS, that would be certainly be intriguing and worth examining.

Continuing on with what Rich mentioned, the question is about the root cause and how the clinical effects are mediated. I agree that the clinical effects are likely due to the reduction of proinflammatory cytokines and reduction of oxidative stress. However the root cause may still be an autoimmune disorder, at least in a subset of patients.

There has never been an autoantibody profiling study done on CFS, with the aim of discovering novel autoantibodies. This study justifies such an investigation in my opinion.

Secondly, there were a few therapies proposed in the following paper: http://www.ncbi.nlm.nih.gov/pubmed/21474251 (Chronic fatigue syndrome A neuroimmunological model, 2011), including anti-TNF drugs. (The TNFs are a class of proinflammatory cytokine)

I think this is a very interesting development, and I want to suggest what I think is going on when Rituximab is used to treat ME/CFS.

It will probably come as no surprise to those familiar with my history here that I will propose a mechanism that fits with the GD-MCB hypothesis for the pathophysiology of ME/CFS.

O.K., here it goes:

Based on the body of immunological studies that have been done in ME/CFS over quite a few years, we know that the immune system is dysfunctional in this disorder. In particular, it has a pronounced shift to the Th2 type of response, away from cell-mediated immunity.

The NK cells and the cytotoxic (CD8) killer-T cells are ineffective, partly because they are unable to produce enough perforin to punch holes in cells that are infected with viruses. Since this is the main mechanism normally used to knock out viral infections, these infections cannot be knocked out.

The immune system is forced to use its fall-back mechanisms, which are the humoral immune response (antibodies produced in Th2 by the B cells, which become plasma cells), and the interferon-induced mechanisms, including RNase-L.

These are less effective and are not able to completely knock out viral infections (The cell-mediated cavalry never arrives). This is the reason for the ongoing guerrilla war in the person's body, with both the reactivated viruses which have been in the body in the latent state, and with new ones that come along and infect the person after the onset of ME/CFS

As has been noted, the B cells do produce proinflammatory cytokines, which of course promote inflammation. Because most PWCs also have a dysfunctional HPA axis, cortisol tends to be low, and the inflammation is allowed to intensify to a higher level than normal.

Note that one of the main features of inflammation is oxidative stress, because cells of the immune system produce oxidizing species to attack the body's enemies. Oxidative stress is well-documented in ME/CFS, with perhaps 20 published papers reporting evidence of it now.

And those familiar with the body's antioxidant system will know that when a state of oxidative stress is present, the antioxidant system is losing the battle between oxidants and antioxidants.

Those familiar will also know that glutathione is the basis of the antioxidant enzyme system in the body. So now we come to realize that in the subset of PWMEs/PWCs in whose bodies infection is a major aspect of their illness, we can expect that a major part of the oxidative stress, and hence a major part of the demand on glutathione, will be due to inflammation, which is being stimulated by the B cells in the overactive Th2 immune response.

O.K., so now we put in Rituximab, which kills the B cells. What happens?

Well, the inflammatory cytokines drop down, as does inflammation. This lowers the oxidative stress, taking a big demand off glutathione, which is then able to rise to at least some degree.

Aficionados of the GD-MCB hypothesis will immediately suspect that a big part of the symptomatology of ME/CFS will diminish, since the causes of a large fraction, perhaps the majority, of ME/CFS symptoms can be traced directly to the depletion of glutathione.

So voila! The patient feels better, until her/his B cells grow back, and the whole process repeats itself, making her/him miserable again. So we hit the patient with another dose of Rituximab, and she/he bounces back up, and so on. If we do succeed in permanently devastating the B cells, what happens in the longer term? Certainly they were there for a purpose. Will the body be adequately defended against its enemies in the future? I think that's a big question.

The main point I want to make is that this treatment, like many others that have been used or proposed for ME/CFS, addresses a down-stream issue in the pathophysiology, and does not get to the root of the problem, which I believe (and have evidence to support this belief) is a vicious circle mechanism that includes glutathione depletion, a functional deficiency of vitamin B12, a partial block of methionine synthase in the methylation cycle, and draining of folates from the cells. So far, the only way it seems to be possible to break this vicious cycle is to lift the partial block in the methylation cycle with appropriate treatment that includes simultaneous use of active forms of folate and high dosage of forms of vitamin B12. Among other effects, this should rebalance the immune system, so that the B cells as well as the other components of the immune system will return to their normal functions. I do need to add that some other things will likely need to be done as well to help this process along, and which things will depend on the details of each case. But lifting the partial methylation cycle block is the fundamental thing that needs to be done.

I would welcome any criticisms of this proposed mechanism. As far as I can tell, everything fits together well.

If anyone wants to get more information on the GD-MCB hypothesis, I recommend watching the video at

The slides from the talk are available there too, if you don't want to hang in for the whole 3-plus hours.

Best regards,

Rich

Click to expand...

Hi, all.

Having now read the full paper, I note that it was reported that two of the patients who received Rituximab, and one who received the placebo (saline solution) were still going strong a year later and were back at full-time work (and by then their B cells had come back up). So how do I explain that? Well, I'm guessing that shutting down the inflammation and the concomitant oxidative stress in the patients who received Rituximab must have given glutathione such a big boost that it was able to break the vicious circle and restore the methylation cycle and the immune system to normal operation by the time the B cells came back up. In the past, I don't know of anyone who was able to turn things around by boosting glutathione, but maybe the inflammation prevented it from going high enough. How about the one who recovered after receiving only saline? I don't know. That's pretty amazing. It's well-known that many PWMEs/PWCs have what has been called a "mild" case of diabetes insipidus (not to be confused with diabetes mellitus), and that involves low blood volume. Putting in some saline has helped a lot of patients temporarily. I don't know how it could produce a permanent fix. So that's a puzzle.

I sure wish these researchers had monitored glutathione in these patients! Note that they write, "Thus, we believe that B-cell depletion targets a central player in the pathogenesis of the CFS disease, directly or indirectly." I suggest that this central player is glutathione.